There are known various conventional methods of chromatographic separation of a starting fluid material containing, for example, 3 components classed as A, B and C into the respective components, representative examples of which include the following six methods:
A method (1) is a batchwise one called "preparatory chromatography," wherein analytical high-performance liquid chromatography is scaled up. However, this is not a method comprising a simulated moving bed operation.
A method (2) is one as disclosed in Japanese Patent Laid-Open No. 124,895/1990, wherein 2-component separation simulated moving bed equipment is used twice. More specifically, this is a method wherein a component A is first separated from a mixture of components B and C in a first step, and the recovered mixed components B and C are then separated from each other in a second step, provided that the partition coefficients of the 3 components are A&lt;B&lt;C for chromatographic packing. The component B having a medium partition coefficient may alternatively be separated together with the component A in the form of a mixture from the component in a first step instead of separation of the components B and C in the form of a mixture from the component A in the first step, followed by separation of the recovered mixed components A and B in a second step. In other words, 2 simulated moving bed chromatographic separators for separating 2 components are prepared or one such separator is used twice for separating 3 components because separation of only 2 components is possible with ordinary simulated moving bed equipment. Incidentally, various known types of separator(s) can be used as the 2-component separation simulated moving bed chromatographic separator(s) to be used in this method.
A method (3) is one disclosed in Japanese Patent Laid-Open No. 227,804/11992 (Japanese Patent Publication No. 24,724/1995). This is a method wherein at least 3 fractions of at least 3 components differing in affinity for packing (hereinafter often referred to simply as "affinity") are continuously separated from one another with one improved simulated moving bed chromatographic separator in a series of operations comprising repeating the step of withdrawing a component B having a medium affinity for packing while feeding desorbent such as eluent and a starting fluid material and the step of withdrawing a component A having a weak affinity for packing and a component C having a strong affinity for packing while feeding eluent.
A method (4) is one disclosed in Japanese Patent Laid-Open No. 10 158,105/1988. This is a method wherein use is made of a fixed bed chromatographic separator.
A method (5) is one disclosed in Japanese Patent Laid-Open No. 232,003/1995.This is a method wherein at least 3 fractions are separated by repeating the step of withdrawing a weak-affinity component A and a medium-affinity component B while feeding eluent and a starting fluid material to simulated moving bed equipment comprising 4 packing bed units, the step of circulating internal liquid through the simulated moving bed without liquid feed and withdrawal, and the step of withdrawing a strong-affinity component C while feeding eluent.
A method (6) is one disclosed in Japanese Patent Laid-Open No. 80,409/1989. In this method, use is made of an arrangement of a plurality of endlessly linked separation columns comprising separation columns packed with a first packing having the following partition coefficients for components: component A &lt;component B &lt;component C, and alternating with separation columns packed with a second packing having the following partition coefficients: component A &lt;component C &lt;component B.
The method (1) is poor in separation performance because it is batchwise, and hence is unfit for industrial-scale separation because a large amount of an expensive high-performance separating packing is necessary to increase the amount of eluent to be used.
The method (2) requires either installing 2 simulated moving bed chromatographic separators or using the same separator twice. Where 2 simulated moving bed chromatographic separators are installed, the equipment cost is high. Where the same separator is used twice, continuous separation of at least 3 components is impossible to pose a problem of poor productivity.
The method (3) requires an increased number of packing bed units for securing sufficient separation in the case of poorly separable components to entail a rise in equipment cost. Thus, what matters is how to secure a sufficient separation performance with as small a number of packing bed units as possible.
The method (4) lacks a simulated moving bed chromatographic separation operation of withdrawing a weak-affinity component A and a strong-affinity component C while always maintaining a circulating flow though it comprises the step of circulating internal fluid through a packing bed with neither fluid feed to the packing bed nor fluid withdrawal from the packing bed. This makes the circulating flow rate so always constant through the packing bed that the weak-affinity component A moves too fast and is therefore liable to catch up with the strong-affinity component C, thereby posing a problem of poor controllability and giving rise to a difficulty in recovering high-purity components.
The method (5) involves such problems that it is liable to be insufficient in separation performance because the number of packing bed units is as small as four, that it is liable to spread the component B through the whole of the system because withdrawal of the fraction B is limited to partial withdrawal of the corresponding effluent, that it is liable to lower the concentrations of the fractions A and C because they are withdrawn in the whole amounts of effluents from the respective packing bed units, and that there exists some of the packing bed not used for separation.
The method (6) involves such an extreme difficulty in choosing and combining packings that it is hard to carry out on an industrial scale.
As described above, various methods according to a fixed bed procedure, a 2-component separation simulated moving bed procedure, a 3-component separation simulated moving bed procedure or the like are known as the conventional chromatographic separation methods of separating at least 3 components. However, there are problems yet to be solved for improvements such as realization of high-purity and high-recovery separation by improving the efficiency of separation and cost reduction of equipment by simplifying and/or miniaturizing it.
Accordingly, an object of the present invention is to provide a chromatographic separation process for chromatographically separating components from a starting fluid material containing at least 3 components, according to which process a simulated moving bed operation capable of exhibiting a high separation performance can be performed even by using the same number of packing bed units as in the conventional methods to materialize a decrease in the amount of used desorbent such as eluent, high-purity recovery of desired substances, and high recoveries of the desired substances.
Another object of the present invention is to provide a chromatographic separation process according to which a simulated moving bed operation capable of exhibiting a high separation performance is possible, so that simulated moving bed equipment smaller in the number of packing bed units than conventional simulated moving bed equipment for separation of at least 3 components can be used to secure purities and recoveries of components comparable to those by the latter.